Pharmacokinetics - Pharmacodynamic Study of HT-2157 in Healthy Subjects and in Patients With Major Depressive Disorder

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dart NeuroScience, LLC
ClinicalTrials.gov Identifier:
NCT01413932
First received: August 4, 2011
Last updated: March 12, 2013
Last verified: March 2013
  Purpose

This is a two part study. The objective of Part 1 is to evaluate the safety, tolerability, and pharmacokinetics of HT-2157 in healthy normal volunteers

Part 2 is a randomized, double-blind, placebo-controlled, multiple (21-day) ascending-dose evaluation of the safety, tolerability, pharmacokinetics, and pharmacodynamics of HT-2157 in patients with major depressive disorder


Condition Intervention Phase
Healthy Volunteers (Part 1)
Major Depressive Disorder (Part 2)
Drug: HT-2157
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: A Two-part Study: Part 1 is a Multiple-dose (7-day), Open-label Evaluation of the Safety, Tolerability, and Pharmacokinetics of HT-2157 in Healthy Subjects. Part 2 is a Randomized, Double-blind, Placebo-controlled, Multiple (21-day) Ascending-dose Evaluation of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HT-2157 in Patients With Major Depressive Disorder

Resource links provided by NLM:


Further study details as provided by Dart NeuroScience, LLC:

Primary Outcome Measures:
  • 7-day plasma PK profile of HT-2157 [ Time Frame: 7-day ] [ Designated as safety issue: No ]
    To assess the multiple dose (7-day) plasma PK profile (including AUC, Cmax, Tmax, T1/2, CL/F, Lambda z, VZ/F) of HT-2157 (and its metabolite) administered in the fed state to healthy male and female subjects

  • To assess the brain penetration of HT-2157 [ Time Frame: 21-days ] [ Designated as safety issue: No ]
    To assess the brain penetration (PK [including Cmax, Tmax, AUC if possible] in cerebrospinal fluid [CSF]) of HT-2157 (and its metabolite)

  • PD profile (CSF and peripheral biomarkers, exploratory biologic and pharmacodynamic markers of potential efficacy) of multiple (21-day) doses of HT-2157 patients with MDD [ Time Frame: 21-days ] [ Designated as safety issue: No ]
    To assess the PD profile (CSF and peripheral biomarkers, exploratory biologic and pharmacodynamic markers of potential efficacy) of multiple (21-day) doses of HT-2157 administered in the fed state to patients with MDD


Secondary Outcome Measures:
  • Safety and tolerability of multiple (7-day) doses of HT-2157 [ Time Frame: 7-days ] [ Designated as safety issue: Yes ]
    To assess the safety and tolerability of multiple (7-day) doses of HT-2157 administered in the fed state to healthy male and female subjects. Change from baseline will be assessed for the following measures: Vital signs, 12-lead ECG, laboratory (hematology, chemistry, urinalysis), physical examinations, and adverse events.

  • Safety and tolerability of multiple (21-day) ascending-doses of HT 2157 [ Time Frame: 21-days ] [ Designated as safety issue: Yes ]
    To assess the safety and tolerability of multiple (21-day) ascending-doses of HT 2157 administered in the fed state to patients with MDD. Change from baseline will be assessed for the following measures: Vital signs, 12-lead ECG, laboratory (hematology, chemistry, urinalysis), physical examinations, and adverse events.

  • 21-day ascending-dose plasma PK profile of HT-2157 [ Time Frame: 21-days ] [ Designated as safety issue: No ]
    To assess the multiple (21-day) ascending-dose plasma PK profile (including AUC, Cmax, Tmax, T1/2, CL/F, Lambda z, VZ/F, RaCmax, RaAUC) of HT-2157 (and its metabolite) administered in the fed state to patients with MDD


Enrollment: 26
Study Start Date: July 2011
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HT-2157 Drug: HT-2157
QD oral dosing
Placebo Comparator: Placebo Drug: Placebo
QD oral dosing

Detailed Description:

This is a two part study. The objective of Part 1 is to evaluate the safety, tolerability, and pharmacokinetics of HT-2157 administered for 7-days in healthy normal volunteers

Part 2 is a randomized, double-blind, placebo-controlled, multiple ascending-dose evaluation of the safety, tolerability, pharmacokinetics of HT-2157 administered for 21-days in patients with major depressive disorder. The primary objective of Part 2 is to assess the CNS penetration of HT-2157 in cerebrospinal fluid. In addition, the potential activity of HT-2157 in this patient population may be assessed using exploratory biologic and pharmacodynamic markers of potential efficacy

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Main Inclusion Criteria (Part 1)

  • No clinically relevant abnormalities
  • Age 18 to 55 years, inclusive
  • Body Mass Index (BMI) of 18.5 to 32 kg/m2

Main Inclusion Criteria (Part 2)

  • No clinically relevant abnormalities
  • Age 18 to 55 years, inclusive
  • Body Mass Index (BMI) of 18.5 to 32 kg/m2
  • Mild-to-Moderate major depressive disorder

Main Exclusion Criteria (Part 1)

- Any disorder that would interfere with the absorption, distribution, metabolism, or excretion of drugs

Main Exclusion Criteria (Part 2)

  • Any disorder that would interfere with the absorption, distribution, metabolism, or excretion of drugs
  • Current and primary Axis I disorder other than MDD
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01413932

Locations
United States, California
Clinical Site
Glendale, California, United States, 91206
Sponsors and Collaborators
Dart NeuroScience, LLC
Investigators
Study Director: Philip Perera, MD Dart NeuroScience, LLC
  More Information

No publications provided

Responsible Party: Dart NeuroScience, LLC
ClinicalTrials.gov Identifier: NCT01413932     History of Changes
Other Study ID Numbers: HT-2157-107
Study First Received: August 4, 2011
Last Updated: March 12, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms

ClinicalTrials.gov processed this record on August 26, 2014